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Biomedical subjects

K Toda

Publications and source records attributed to K Toda.

At least 55 records · Page 3Linked to original sources

Altered expression of fatty acid-metabolizing enzymes in aromatase-deficient mice.

Hepatic steatosis is a frequent complication in nonobese patients with breast cancer treated with tamoxifen, a potent antagonist of estrogen. In addition, hepatic steatosis became evident spontaneously in the aromatase-deficient (ArKO) mouse, which lacks intrinsic estrogen production. These clinical and laboratory observations suggest that estrogen helps to maintain constitutive lipid metabolism. To clarify this hypothesis, we characterized the expression and activity in ArKO mouse liver of enzymes involved in peroxisomal and mitochondrial fatty acid beta-oxidation. Northern analysis showed reduced expression of mRNAs for very long fatty acyl-CoA synthetase, peroxisomal fatty acyl-CoA oxidase, and medium-chain acyl-CoA dehydrogenase, enzymes required in fatty acid beta-oxidation. In vitro assays of fatty acid beta-oxidation activity using very long (C24:0), long (C16:0), or medium (C12:0) chain fatty acids as the substrates confirmed that the corresponding activities are also diminished. Impaired gene expression and enzyme activities of fatty acid beta-oxidation were restored to the wild-type levels, and hepatic steatosis was substantially diminished in animals treated with 17beta-estradiol. Wild-type and ArKO mice showed no difference in the binding activities of the hepatic nuclear extracts to a peroxisome proliferator response element. These findings demonstrate the pivotal role of estrogen in supporting constitutive hepatic expression of genes involved in lipid beta-oxidation and in maintaining hepatic lipid homeostasis.

Acyl-CoA Dehydrogenase↗

Subjective sensation of heaviness in gout patients.

The main objective of the treatment of gout is to protect the major organs. Almost all gout patients require medication throughout their lives. Gout patients are asymptomatic during intercritical periods, even if they are not receiving antihyperuricemic drugs. Some patients, therefore, misinterpret that their gout is cured and may cease taking medication of their own accord. Thirty-two gout patients who had received continuous treatment with antihyperuricemic drugs for more than 3 months were selected. The sensation of heaviness was relieved by antihyperuricemic drugs in 14 (44%) of 32 patients. The heaviness did not exist or change in the other patients. Benzbromarone, probenecid, and allopurinol were found to be effective. The sensation of heaviness occurred after increased physical activity in 10 of 14 patients. Of 14 patients, 12 did not notice that the sensation of heaviness was relieved by antihyperuricemic drugs. Two hypotheses for the cause of heaviness are considered. One is mild gouty neuropathy, the other low-grade inflammation. A proper understanding that this symptom is relieved by antihyperuricemic drugs may serve as additional motivation for gout patients to take their medication regularly.

Adult↗

Bilateral simultaneous oblique MR imaging of the proximal femur.

Oblique axial and oblique coronal MR images parallel to the femoral neck provide more valuable information concerning the proximal femur than orthogonal images. The main disadvantage of the unilateral oblique imaging is that the imaging time is significantly increased when both hips need to be imaged. If the bilateral oblique imaging is performed simultaneously, this increase in imaging time is eliminated because the scanning time for the bilateral oblique imaging and the orthogonal imaging is the same.

Female↗

Nociceptive responses and immunohistochemical changes in the rat brain under gravity stress.

It is well known that exposure to various stresses leads to pain suppression in animals. However, there is no report about the effects of gravitational alteration to serve as a kind of stress. The purpose of the present study is to clarify the effect of hypergravity (2 G) on the nociceptive responses and histochemical changes in rats. We examined the level of the threshold of withdrawal reflex against the noxious [correction of noxicious] stimulation in rats that were exposed to 2 G. Data show that the 2 G exposure elevates the nociceptive threshold. We have demonstrated for the first time that gravity change induces analgesic effects on rats in concomitant with c-fos induction in the arcuate, and paraventricular nuclei of rat hypothalamus. Gravity change acts as a kind of stress in rats.

Analgesia↗

Patch clamp studies on V-type ATPase of vacuolar membrane of haploid Saccharomyces cerevisiae. Preparation and utilization of a giant cell containing a giant vacuole.

A method for obtaining giant protoplasts of Escherichia coli (the spheroplast incubation (SI) method: Kuroda et al. (Kuroda, T., Okuda, N., Saitoh, N., Hiyama, T., Terasaki, Y., Anazawa, H., Hirata, A., Mogi, T., Kusaka, I., Tsuchiya, T., and Yabe, I. (1998) J. Biol. Chem. 273, 16897-16904) was adapted to haploid cells of Saccharomyces cerevisiae. The yeast cell grew to become as large as 20 micrometer in diameter and to contain an oversized vacuole inside. A patch clamp technique in the whole cell/vacuole recording mode was applied for the vacuole isolated by osmotic shock. At zero membrane potential, ATP induced a strong current (as high as 100 pA; specific activity, 0.1 pA/micrometer(2)) toward the inside of the vacuole. Bafilomycin A(1,) a specific inhibitor of the V-type ATPase, strongly inhibited the activity (K(i) = 10 nM). Complete inhibition at higher concentrations indicated that any other ATP-driven transport systems were not expressed under the present incubation conditions. This current was not observed in the vacuoles prepared from a mutant that disrupted a catalytic subunit of the V-type ATPase (RH105(Deltavma1::TRP)). The K(m) value for the ATP dose response of the current was 159 microM and the H(+)/ATP ratio estimated from the reversible potential of the V-I curve was 3.5 +/- 0.3. These values agreed well with those previously estimated by measuring the V-type ATPase activity biochemically. This method can potentially be applied to any type of ion channel, ion pump, and ion transporter in S. cerevisiae, and can also be used to investigate gene functions in various organisms by using yeast cells as hosts for homologous and heterogeneous expression systems.

Anti-Bacterial Agents↗

Identification of optimal conditions for lung graft storage with Euro-Collins solution by use of a rat orthotopic lung transplant model.

BACKGROUND: Lung preservation disrupts normal vascular homeostasis, resulting in increased permeability, vasoconstriction, and endothelial cell adhesion for neutrophils. We hypothesized that a storage strategy that best preserves post-lung transplantation (LTX) vascular homeostasis might be organ and species specific. Because of the potential utility of a rat LTX model for developing improved lung preservation strategies, we have attempted to identify the optimal physical conditions for rat lung graft storage. METHODS AND RESULTS: Conditions that were tested included harvest inflation pressure (0, 10, or 20 mm Hg), inflation gas composition (100% N(2), room air, or 100% O(2)), and storage temperature (4 degrees, 10 degrees, or 15 degrees C). Modified Euro-Collins solution served as the base preservation solution for all experiments, with a preservation duration of 4 to 6 hours. Arterial oxygenation (PaO(2), mm Hg), pulmonary vascular resistance (mm Hg/mL per minute), recipient survival (%), and graft neutrophil infiltration (DeltaAbs(460 nm)/min) were measured 30 minutes after transplantation of the left lung and exclusion of the right lung from the circulation. All tested conditions significantly affect post-LTX vascular homeostasis. Inflation at 10 mm Hg pressure preserved lungs significantly better than did other pressures. There was a tendency for room air to improve all measured variables compared with 100% N(2) or 100% O(2) and a significant improvement in recipient survival with room air storage. Of the 3 storage temperatures investigated, 10 degrees C storage provided the best preservation in terms of PaO(2), graft neutrophil infiltration, and survival. CONCLUSIONS: We conclude that storage at 10 degrees C, 10 mm Hg inflation pressure, with room air establishes optimal lung storage conditions with Euro-Collins solution in this rat LTX model. These data suggest that these conditions should be used to evaluate new and potentially improved preservation strategies.

Animals↗

Kinetic Study on the Formation of Colloidal Gold in the Presence of Acetylenic Glycol Nonionic Surfactant.

The formation of colloidal gold was kinetically studied using the monomer or micelle form of the acetylenic glycol nonionic surfactant Surfynol 465, which functions as a reducing and stabilizing agent. When two equal volumes of aqueous solution of Au(III) and Surfynol 465 were mixed, absorbance at the peak around 300 nm due to Au(III) rapidly decreased with time exponentially. A new peak began to appear around 530 nm, whose height sigmoidally increased with time, showing the formation of colloidal gold. From the variation in absorbance at 300 or 530 nm with time, colloidal gold formation would appear to occur through consecutive first-order reactions, Au(III) --> Au(I) --> Au(0) --> gold particle, for monomer and micelle systems. As for Au(I), the complex between Au(I) and &bond;C&tbond;C&bond; of Surfynol 465 was assigned based on reactions previously proposed for the Raman spectra of colloidal gold (Sato, S., Colloid Polym. Sci. 274, 1161 (1996)). The reaction, Au(0) --> gold particle, proceeded quickly. The overall rate of reaction was slower in the micelle system than in the monomer system. For both systems, the rate constant of the reaction Au(III) --> Au(I) exceeded the constant of the reaction Au(I) --> Au(0), and the activation energies of the two reactions were 58 kJ mol(-1). From the agreement with the activation energy of formation of colloidal gold by another method, consecutive first-order reactions, Au(III) --> Au(I) --> Au(0) --> gold particle, were considered valid for the formation of colloidal gold in the presence of Surfynol 465. Copyright 1999 Academic Press.

Journal Article↗

Correlation of antiangiogenic and antitumor efficacy of N-biphenyl sulfonyl-phenylalanine hydroxiamic acid (BPHA), an orally-active, selective matrix metalloproteinase inhibitor.

The antiangiogenic activity and antitumor efficacy of a newly developed matrix metalloproteinase (MMP) inhibitor were examined. N-biphenyl sulfonyl-phenylalanine hydroxiamic acid (BPHA) potently inhibits MMP-2, -9, and -14, but not MMP-1, -3, or -7. In contrast, (-)BPHA, an enantiomer of BPHA, was inactive against all MMPs tested. Daily oral administration of 200 mg/kg BPHA, but not (-)BPHA in mice resulted in potent inhibition of tumor-induced angiogenesis, primary tumor growth, and liver metastasis. The growth inhibition activity of BPHA was 48% and 45% in a B16-BL6 melanoma and F2 hemangio-endothelioma model, respectively. BPHA also showed 42% inhibition of the liver metastasis of C-1H human colon carcinoma cells. These results indicate that selective MMP inhibition is correlated with antiangiogenic and antitumor efficacy and that the selective MMP inhibitor BPHA has therapeutic potential.

Animals↗

Colocalization of phospholipase D1 and GTP-binding-defective mutant of ADP-ribosylation factor 6 to endosomes and lysosomes.

Phospholipase D (PLD) is involved in various aspects of cellular function. Two isoforms, PLD1 and PLD2, have been identified. PLD1, which has two splicing variants, is regulated by various factors, including ADP-ribosylation factor (ARF). We here show that both variants of PLD1 are predominantly localized to late endosomes and lysosomes, but not to the Golgi apparatus or endoplasmic reticulum in contrast to earlier studies. Furthermore, PLD1s show significant colocalization with an ARF6 mutant defective in GTP binding. The data suggest that PLD1, under the regulation of ARF6, plays a role in the function of endosomes and lysosomes.

ADP-Ribosylation Factor 6↗

Superior protection in orthotopic rat lung transplantation with cyclic adenosine monophosphate and nitroglycerin-containing preservation solution.

BACKGROUND: Primary lung graft failure is common, and current lung preservation strategies are suboptimal. Because the decline in lung levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate during preservation could enhance adhesiveness of endothelial cells for leukocytes as well as increase vascular permeability and vasoconstriction, we hypothesized that buttressing these levels by means of a preservation solution would significantly improve lung preservation. METHODS: An orthotopic rat left lung transplantation model was used. Lungs were harvested from male Lewis rats and preserved for 6 hours at 4 degrees C with (1) Euro-Collins solution (n = 8); (2) University of Wisconsin solution (n = 8); (3) low-potassium dextran glucose solution (n = 8); (4) Columbia University solution (n = 8), which contains a cyclic adenosine monophosphate analog (dibutyryl cyclic adenosine monophosphate) and a nitric oxide donor (nitroglycerin) to buttress cyclic guanosine monophosphate levels; or (5) Columbia University solution without cyclic adenosine monophosphate or nitroglycerin (n = 8). PaO2, pulmonary vascular resistance, and recipient survival were evaluated 30 minutes after left lung transplantation and removal of the nontransplanted right lung from the pulmonary circulation. RESULTS: Among all groups studied, grafts stored with Columbia University solution demonstrated the highest Pa O2 (355 +/- 25 mm Hg for Columbia University solution versus 95 +/- 22 mm Hg for Euro-Collins solution, P <.01, 172 +/- 55 mm Hg for University of Wisconsin solution, P <.05, 76 +/- 15 mm Hg for low-potassium dextran glucose solution, P <.01, and 82 +/- 25 mm Hg for Columbia University solution without cyclic adenosine monophosphate or nitroglycerin, P <.01) and the lowest pulmonary vascular resistances (1 +/- 0.2 mm Hg * mL-1 * min-1 for Columbia University solution versus 12 +/- 4 mm Hg * mL-1 * min-1 for Euro-Collins solution, P <.01, 9 +/- 2 mm Hg * mL-1 * min-1 for University of Wisconsin solution, 14 +/- 6 mm Hg * mL-1 * min-1 for low-potassium dextran glucose solution, P <.01, and 8 +/- 2 mm Hg * mL-1 * min-1 for Columbia University solution without cyclic adenosine monophosphate and nitroglycerin). These functional and hemodynamic improvements provided by Columbia University solution were accompanied by decreased graft leukostasis and decreased recipient tumor necrosis factor alpha and interleukin 1alpha levels compared with the other groups. In toto, these improvements translated into superior survival among recipients of Columbia University solution-preserved grafts (100% for Columbia University solution, 37% for Euro-Collins solution, P <.01, 50% for University of Wisconsin solution, P <.05, 50% for low-potassium dextran glucose solution, P <.05, and 13% for Columbia University solution without cyclic adenosine monophosphate and nitroglycerin, P <.01). CONCLUSION: Nitroglycerin and cyclic adenosine monophosphate confer beneficial vascular effects that make Columbia University solution a superior lung preservation solution in a stringent rat lung transplantation model.

Adenosine↗

Analysis of flow behavior of non-Newtonian fluids based on a concept of traveling force.

The non-Newtonian flow behavior of a culture fluid with suspended adhesive particles of microbes and polysaccharides is analyzed in this study based on a new concept. The concept assumes that the force generated by the contact between particles under shearing flow due to mixing is decreasingly transmitted through the fluid in radial directions. A viscosity equation that includes the degree of force transmisson is derived by considering the shear stress to the force. On the other hand, the shear stress dependence on the concentration of bound particles is expressed in an equation by introducing an effective shear stress that works on the contact sites of the bindings and varies the concentration. Relating the degree of force transmission to the concentration derives a non-Newtonian viscosity equation in terms of shear stress (or shear rate), in which zero-shear viscosity is correlated with both the particle concentration and molecular weight of polymers. It is confirmed that calculations based on the equation are in good agreement with experimental results previously reported for aqueous solutions of several polysaccharides.

Journal Article↗

Pseudolymphoma syndrome due to carbamazepine.

We described a 29-year-old Japanese woman with a pseudolymphoma syndrome due to carbamazepine. Physical examination revealed a diffuse erythematous papular eruption over almost all of her body with generalized lymphadenopathy. Histopathologic examination disclosed histology compatible with the nodular pattern of pseudo-T-cell lymphoma. The Southern blot analysis did not disclose the monoclonality of the gamma T cell recepter gene. We consider that it is very important to recognize this pseudolymphoma syndrome due to carbamazepine to avoid possibly subjecting the patient to unnecessary chemotherapy.

Adult↗

[Elevation of serum and urine tumor necrosis factor levels after transurethral resection of the prostate].

BACKGROUND: Recent studies have suggested that inflammatory cytokines are major mediator of the acute phase protein response after surgery. The aim of the present study is to investigate the relationship between the degree of surgical trauma and the change of serum and urine cytokine levels after transurethral resection of the prostate (TUR-P). METHOD: Serum and urine concentrations of tumor necrosis factor-alpha (TNF), interleukin-6 (IL 6), and interleukin-1 (IL 1) were evaluated in 55 patients who underwent TUR-P and in 23 patients who underwent abdominal surgery. The samples were collected periodically before and after an intervention, and the concentrations of cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: The concentration of serum TNF was significantly increased 6 hours after TUR-P. Since serum TNF level was not increased after abdominal surgery, serum TNF level was significantly higher after TUR-P than after abdominal surgery. Serum IL 6 and IL 1 levels were not increased after TUR-P. Urine levels of TNF, IL 6 and IL 1 were significantly increased after TUR-P, meanwhile no significant elevation of urine cytokine levels was recognized in the patients who underwent abdominal surgery. The elevation of urine cytokine levels was thought to be caused by the increased production of cytokines at the surgically resected sites. The urine TNF level after TUR-P was increased related to the resected tissue volume and irrigation fluid volume. The preoperative urinary tract infection caused excessive elevation of the urine TNF level after TUR-P. The urine TNF level after TUR-P also tended to be increased depending on the degree of postoperative pyrexia. CONCLUSION: These results indicate the unique response of TNF to TUR-P. Measurement of serum and urine TNF levels after TUR-P can be a useful index for evaluating the perioperative condition of the patients undergoing TUR-P.

Adult↗

[A case of Behçet's disease presenting cerebral infarction due to occlusions of the bilateral internal carotid arteries].

This is a case report of a 41-year-old man with Behçet's disease who suffered from cerebral infarction due to complete occlusions of the bilateral internal carotid arteries. His illness began at age 23 with blurred vision of the right eye. The last few years he complained of recurrent painful ulcers on the mucosa or skin of the mouth and the external genitalia. In August 1998, he was admitted to our hospital in an acute confusional state with right hemiplegia. Head CT scans and MRIs revealed acute and subacute ischemic lesions in the left frontal lobe and some other regions of the bilateral hemispheres. Carotid angiography showed complete occlusions of the bilateral internal carotid arteries just rostral to the bifurcations. He did not have any histories of hypertension nor other risks for cerebrovascular diseases. Although direct evidence for the cause of carotid occlusions was not obtained, we speculated that his cervical lesions came from the arterial changes attributable to vasculo-Behçet's disease. Vascular involvements are not infrequent in Behçet's disease, but we believe such occlusive lesions in the bilateral internal carotid arteries as seen in our case are extremely rare. As a construction worker he had undergone a lot of mechanical stress on his neck, which might be a trigger for the carotid lesions.

Adult↗

[A case of Sweet's syndrome (acute febrile neutrophilic dermatosis) showing transient jargon aphasia].

A 54-year-old woman visited our emergency service complaining of a severe language disturbance. She was fluently speaking something but most of the words were merely meaningless syllables. This jargon state lasted only four hours, then her abnormal speech rapidly and completely recovered within 24 hours. She had also suffered from painful oral ulcers, fever and erythema-like eruptions on her face for about three weeks. Skin biopsy of a facial lesion revealed a dense infiltrate of neutrophils in the dermis and minimal features of vasculitis, which, with other typical clinical findings, led us to the diagnosis of Sweet's syndrome. Although head CT scans, MRIs, MRA or SPECT could not detect any brain lesions, a cerebrospinal fluid examination showed a mild pleocytosis of 38/mm3 with 47% polymorphonuclear cells. There have been a few case reports on Sweet's syndrome accompanying neurologic symptoms, most of which are mild meningitis. We speculate that the transient aphasia was due to a focal lesion in the central nervous system attributable to Sweet's syndrome. Sweet's syndrome might bring inflammatory or ischemic lesions to the cerebrum as Behçet's disease.

Acute Disease↗

Characterization of a chloroplast isoform of serine acetyltransferase from the thermo-acidiphilic red alga Cyanidioschyzon merolae.

We isolated a gene for serine acetyltransferase (SAT), a key enzyme in sulfate assimilation, from the primitive red alga Cyanidioschyzon merolae, an inhabitant of sulfurous hot springs, and designated this gene cmSAT. The N-terminal region of the cmSAT protein has characteristics of a chloroplast targeting peptide. cmSAT protein fused with a 6x histidine tag complemented a SAT deficient Escherichia coli mutant. The protein was purified with its SAT activity, which was inhibited by cysteine, using the high affinity of the histidine tag in an Ni-NTA column. The Km values for acetyl-CoA and l-serine were 0.3 and 0.1 mM, respectively. Southern blotting indicated the existence of other SAT isoforms in C. merolae. A 2.4 kb transcript was always detected when growth was synchronized under a 12-h light/dark cycle. Under these conditions, a 31-kDa protein was always detected on immunoblots, indicating processing of the cmSAT protein and constitutive expression of cmSAT. A 45-kDa protein, thought to be the unprocessed cmSAT protein, was detected in the dark period, from M phase to early G1 phase. No significant change in the level of protein expression was detected under continuous darkness or in a sulfate-deficient medium. Using immunoelectron microscopy, the cmSAT protein was primarily detected in the stroma and a few were detected in the cytoplasm, which indicate that cmSAT protein is transported to and functions in a chloroplast.

Acetyltransferases↗